Metallic nanoparticles as orthopedic biomaterial

ABSTRACT

A composition for use as a prosthetic biomaterial and associated method. The biomaterial exhibits cytocompatibility, mechanical functionality and osteoblast adhesion between the implant and interfacing surface. The biomaterial is metallic, has a grain size less than about 500 nanometers and has a surface roughness of less than about 800 nm rms.

CROSS REFERENCE TO RELATED APPLICATION

This application is a U.S. national counterpart application ofinternational application serial No. PCT/US2004/009358 filed Mar. 26,2004, which claims priority to U.S. Provisional Patent Application No.60/458,227 filed Mar. 27, 2003.

GOVERNMENT RIGHTS

Research relating to this invention was supported in part by the UnitedStates Government under Grant No. DMI0232597 awarded by the NationalScience Foundation. The U.S. Government may have certain rights in thisinvention.

FIELD OF THE INVENTION

This invention relates to a composition for use as a biomaterial fororthopedic implants and associated method and more particularly to aprosthetic biomaterial that includes metallic nanoparticles.

BACKGROUND OF THE INVENTION

Biomaterials, commonly used as implantable orthopedic prosthetic devicesare not designed to retain functionality while maintaining compatibilitywith respect to biological factors at the implant/tissue interface. Inorder to achieve cytocompatability, it is desirable that the biomaterialsurface characteristics at the interface be optimally compatible withpertinent bone cell types. Achieving similar mechanical properties tonative tissue insures limited destruction of local cells. The surfacetexture of the biomaterial is also important to control for orthopedicimplant efficacy to closely harmonize the mass and kinetics of theosseous biomolecular events. Previously implantable devices have beenfabricated of ceramic, polymer, composite and metallic materials.

Metallic materials which have been used include titanium (Ti), atitanium alloy and a cobalt chromium molybdenum. These metallicmaterials have been found to have a grain size on the order of microns(μm).

Implant failures have been observed with each of these materials.Investigations have been run for the purpose of finding a technique foreliminating or at least reducing the incidents of bone implant failuresin humans. The underperformance of implant has been blamed on incompleteosseointegration (i.e., lack of bonding of an orthopedic implant to ajuxtaposed bone), stress shielding and/or the generation of wear debrisat articulating surfaces.

Thus, it is desirable to increase the adhesion between the implant andtissue surface (sometimes referred to as osteoblast adhesion)particularly in connection with the metallic surfaces so as to addressimplant feature issues.

SUMMARY OF THE INVENTION

Biomaterials are commonly used in implantable orthopedic prostheticapplications are not designed to retain functionality while maintainingcompatibility with respect to biological factors at the implant/tissuesurface. In order to achieve cytocompatibility, it is desirable that thebiomaterial surface characteristics at the interface be optimallycompatible with the pertinent bone cell types. Achieving similarmechanical properties to native tissues insures limited destruction oflocal cells. The surface texture of the biomaterial is also important tocontrol for orthopedic implant efficacy to closely harmonize with themass and kinetics of osseous biomolecular events.

It has been found that osteoblast adhesion or adhesion at themetal/tissue interface can be increased by utilizing nanoparticlemetals. These metals have a nanosize of less than 500 nm (nanometers)and usually between about 200 and 500 nm (nanometers). At this nanosize, the metallic particles are similar in size to the cell size of thetissue under consideration. Moreover these metals have a surfaceroughness measured in rms nanometers of between about 11 and 360 nm rms.However, the roughness can be as great as 800 nm rms. In particular,titanium based metals such as commercially pure titanium, a titaniumalloy (on a weight basis 11% Ti, 39% Al and 50% V) and a cobalt chromemolybdenum alloy (on a weight basis 3% Co 70% Cr and 27% Mo) can besuccessfully utilized. The composition of these metals on an atomicratio basis can be expressed as Ti-6Al-4V and Co-28Cr-6Mo.

DETAILED DESCRIPTION

While the embodiments disclosed herein are susceptible to variousmodifications and alternative forms, specific embodiments will herein bedescribed in detail. It will be understood, however, that there is nointent to limit the disclosure to the particular forms described, but onthe contrary, the intention is to cover all modifications, equivalentsand alternatives falling within the spirit and scope of the disclosure.

The current disclosure involves the use of nanoparticles of variousmetals such as titanium, titanium alloy (11% Ti, 89% Al and 80% V) andcobalt-chromium-molybdenum (3% Cr, 70% Cr and 27% Mo). Nanoparticles(less than 500 nm) having a surface roughness on the order of 11-356 rmsnanometers have a high surface reactivity with tissue cells. Asindicated above, the roughness can be up to 500 nm rms. In theirproperly consolidated form, nanoparticles result in increased elasticmodules and strength as well as in nanostructured grains. These materialformulations contain highly developed crystal grains fabricated out oftheir corresponding nanoparticles and possess properties(cytocompatibility and mechanical) that are appropriate for differentorthopedic applications to the skeletal system. Most importantly, thenanophase metals significantly increase functions of cells that areresponsible for bone adhesion (osteoblast adhesion) and bone tissueregeneration. Significantly increased adhesion and differentiation ofbone cells as well as mineralization of the tissue are desirable toresult in efficient and effective implants. For these reason, metallicnanoparticles are desirable as they closely match the mass and kineticsof bone/bodily fluid biomolecular reactions and enhance osseosusfunctions.

Nano size metal particles are available as a powder, formed by vapordeposition techniques and can be purchased from Power Tech Associates,31 Flagship Drive, North Andover, Mass. 01845-6194. More specifically,these powders can include commercially pure titanium, the titanium alloy(such as Ti6Al4V) and the cobalt chrome molybdenum alloy 27%(Co-28Cr-6Mo). The material characteristics are shown in the Tablebelow.

Surface Roughness (RMS in ASTM Materials Particle Size Nanometers)DESIGNATION Ti 500 Nanometers 11.9 F-67; G2 Ti6Al4V 500 Nanometers 15.2F-136 Co 28 Cr6 MO 200 Nanometers 356 F-75; F-799

The powders indicated above can be commercially obtained.

These powders were obtained and loaded into a steel die and pressed atroom temperature. One pressure, 10 giga pascals was used to press thetitanium based compacts to a green density of 90-95%. Thecobalt-chrome-molybdenum material was pressed at 5 giga pascals for 5minutes to achieve the green density indicated above. The green diskswhich were produced by pressing were approximately 12 millimeters indiameter and between 0.50 and 1.1 millimeters thick. The surfacecharacteristics of these metal compacts were characterized usingscanning electromicroscopy (SEM) and atomic force microscopy (AFM)techniques. Using these techniques, the surface roughness wascharacterized using root mean square values expressed in nanometers aspointed out above.

Using these materials, osteoblast adhesion was determined. The generaltechnique was to use human osteoblasts (bone forming cells; CLR 1137zAmerican Culture Collection Population Nos. 6-12) which were seeded ontothe substrates of interest and placed in standard cell cultureconditions. That is a humidified, 5% Co2, 95% air environment for 1-3hours. After the prescribed times, the substrates were rinsed, theremaining cells fixed and the remaining cells then examined and countedunder a fluorescent microscope. Osteoblast morphology and adhesionlocations of interest were examined using a scanning electron microscope(SEM).

The tests indicated an increased osteoblast adhesion to the nano sizedparticles and having a surface roughness indicated above. Particularly,it appeared that the osteoblasts formed on the grain boundaries of thematerials. It is believed that the number of grain boundaries wasincreased due to the smaller size of the particles and the surfacetexture.

It has therefore been concluded that materials of a nanoparticle sizeand particularly having a texture as indicated above, increased theosteoblast formation and adhesion. The metals, more specifically thetitanium titanium based alloys and cobalt based alloys) in powder formare believed to enhance implantation. It is appreciated that the powdermaterial can be subjected to the various heat treatments and sinteringprocesses of powder metallurgy. Moreover, the materials can be formedeither as a unit or as a surface on a substrate in which surfaceinterfaces with tissue.

While the disclosure has been illustrated and described in detail in theforgoing is considered to be as exemplary and not restrictive incharacter, it being understood that the illustrative embodiments havebeen described and it all changes in modifications that come within thespirit and scope of this disclosure are desired to be protected.

1. A biomaterial for use in implantable orthopedic prosthetic deviceswherein said biomaterial comprises consolidated nanoparticles and a.exhibits cytocompatibility with interfacing biological cells; b.exhibits mechanical functionality with interfacing biological cells; c.exhibits osteoblast adhesion between the implant and the interfacingbiological cells; wherein the biomaterial d. is a metal; e. has a grainsize less than about 500 nanometers; and f. has a surface roughness lessthan about 500 nanometers root mean square (nm rms).
 2. A biomaterial asin claim 1 wherein the surface roughness is between 11 and 356nanometers root mean square.
 3. A biomaterial as in claim 2 whichconsists essentially of a titanium based metal.
 4. A biomaterial as inclaim 3 wherein the titanium based metal has a particle size of lessthan about 500 nanometers and a surface roughness of about 11 nanometersroot mean square.
 5. A biomaterial as in claim 4 wherein said titaniumbased metal is commercially pure titanium.
 6. A biomaterial as in claim1 wherein said metal is a titanium based alloy consisting essentiallyof, on a weight percent basis, of about 11% titanium, 39% aluminum and50% vanadium.
 7. A biomaterial as in claim 1 wherein the metal, on aweight percent basis, is a cobalt-chrome-molybdenum alloy consistingessentially of about 3% cobalt, 70% chromium and 27% molybdenum with theparticle size less than about 200 nanometers and the surface roughnessless than about 356 nanometers root mean square.
 8. A biomaterial as inclaim 1 wherein said metal is a powder.
 9. A biomaterial as in claim 8wherein said powder is consolidated and compressed so as to form asurface for interfacing with biological tissue.
 10. A biomaterial as inclaim 8 wherein said powder is compressed at room temperature.
 11. Amethod of forming an implantable orthopedic prosthetic device includingthe steps of: (a) providing a metal biomaterial in powder form;
 1. whichexhibits cytocompatibility within interfacing biological cells; 2.exhibits mechanical functionality with interfacing biological cells; and3. exhibits osteoblast adhesion between the implant and interfacingbiological cells; (b) compressing the powder in the absence of bindersor sintering temperatures so as to form a consolidated compositioncomprising a surface for interfacing with biological cells, saidconsolidated composition having a grain size less than about 500nanometers; and a surface roughness between about 11 and 360 nanometersroot mean square.
 12. A biomaterial for use in implantable orthopedicprosthetic devices wherein said biomaterial comprises consolidatednanoparticles and a. exhibits cytocompatibility with interfacingbiological cells; b. exhibits mechanical functionality with interfacingbiological cells; c. exhibits osteoblast adhesion between the implantand the interfacing biological cells; wherein the biomaterial d. is ametal; and e. has a particle size between 200 and 500 nanometers and asurface roughness between 11 and 360 nanometers root mean square.
 13. Abiomaterial for use in implantable orthopedic prosthetic devices whereinsaid biomaterial: a. exhibits cytocompatibility with interfacingbiological cells; b. exhibits mechanical functionality with interfacingbiological cells; c. exhibits osteoblast adhesion between the implantand the interfacing biological cells; wherein the biomaterial d. is ametal; e. has a particle size less than 500 nanometers, and f. has asurface roughness less than 500 nanometers root mean square (nm rms).14. A biomaterial as in claim 13 wherein the surface roughness isbetween 11 and 356 nanometers root mean square.
 15. A biomaterial as inclaim 14 which consists essentially of a titanium based metal.
 16. Abiomaterial as in claim 13 wherein the metal on a weight percent basis,is a cobalt-chrome-molybdenum alloy consisting essentially of about 3%cobalt, 70% chromium and 27% molybdenum with the surface roughness lessthan about 356 nanometers root mean square.